ABSTRACT
OBJECTIVES: Dopamine-replacement utilizing L-DOPA is still the mainstay treatment for Parkinson's disease (PD), but often leads to development of L-DOPA-induced dyskinesia (LID), which can be as debilitating as the motor deficits. There is currently no satisfactory pharmacological adjunct therapy. The endogenous opioid peptides enkephalin and dynorphin are important co-transmitters in the direct and indirect striatofugal pathways and have been implicated in genesis and expression of LID. Opioid receptor antagonists and agonists with different selectivity profiles have been investigated for anti-dyskinetic potential in preclinical models. In this study we investigated effects of the highly-selective µ-opioid receptor antagonist CTAP (> 1200-fold selectivity for µ- over δ-opioid receptors) and a novel glycopeptide congener (gCTAP5) that was glycosylated to increase stability, in the standard rat LID model. RESULTS: Intraperitoneal administration (i.p.) of either 0.5 mg/kg or 1 mg/kg CTAP and gCTAP5 completely blocked morphine's antinociceptive effect (10 mg/kg; i.p.) in the warm water tail-flick test, showing in vivo activity in rats after systemic injection. Neither treatment with CTAP (10 mg/kg; i.p.), nor gCTAP5 (5 mg/kg; i.p.) had any effect on L-DOPA-induced limb, axial, orolingual, or locomotor abnormal involuntary movements. The data indicate that highly-selective µ-opioid receptor antagonism alone might not be sufficient to be anti-dyskinetic.
Subject(s)
Dyskinesia, Drug-Induced/drug therapy , Levodopa/adverse effects , Narcotic Antagonists/therapeutic use , Receptors, Opioid, mu/antagonists & inhibitors , Animals , Disease Models, Animal , Glycopeptides/pharmacology , Male , Morphine/pharmacology , Nociception/drug effects , Rats, Sprague-Dawley , Receptors, Opioid, mu/metabolismABSTRACT
Clinical trials are extremely difficult to undertake and recruiting patients for these trials is one of the most significant challenges. This brief report sought to determine the suitability of an urgent care center as a research recruitment site by assessing its patients' views on participating in clinical trials. One thousand and two subjects were surveyed over a 45-day period; 9.0 % had previously participated in clinical trials while 46.6 % indicated they would be interested in participating in future clinical trials if given the opportunity. This research suggests that the urgent care venue is a viable recruitment source for clinical trials.
Subject(s)
Ambulatory Care Facilities , Ambulatory Care , Patient Selection , Randomized Controlled Trials as Topic/methods , Humans , Internet , Patient Acceptance of Health Care , Patients/psychology , Perception , Research Subjects/psychology , Surveys and QuestionnairesABSTRACT
BACKGROUND: Cortical spreading depression (CSD) is a wave of depolarization followed by depression of bioelectrical activity that slowly propagates through the cortex. CSD is believed to be the underlying mechanism of aura in migraine; however, whether CSD can elicit pain associated with migraine headache is unclear. METHODS: Awake, freely moving rats were monitored for both CSD events and behavioral responses resulting from dural-cortical pinprick and/or KCl injection to the occipital cortex. RESULTS: We observed tactile allodynia of the face and hindpaws, as well as enhanced Fos expression within the trigeminal nucleus caudalis (TNC) following CSD induced by KCl injection into the cortex, but not by pinprick. Application of KCl onto the dura elicited cutaneous allodynia and increased Fos staining in the TNC but did not elicit CSD events. CONCLUSIONS: These data suggest that sustained activation of trigeminal afferents that may be required to establish cutaneous allodynia may not occur following CSD events in normal animals.